Brain Scans Detect Earliest Stages Of Alzheimer's Disease

"We have found a way to measure what may be the earliest changes in the memory-processing areas of the brain," says Dr. Mony de Leon, Professor of Psychiatry at NYU School of Medicine. "Our technique can be performed rapidly and potentially may be used to monitor the effect of therapies on the course of Alzheimer's disease," says Dr. de Leon, who is Director of the NYU School of Medicine Neuroimaging Research Laboratory.

In a new study published in the Jan. 2 issue of the journal Lancet, Dr. de Leon and co-workers report that they have measured the anatomical changes in a key memory center of the brain called the entorhinal cortex. They demonstrate through MRI scans that this area shrinks substantially in patients with very mild Alzheimer's compared to healthy volunteers. MRI scans are a powerful imaging tool that rely on electromagnetic energy to excite water molecules in the brain in order to create an anatomical snapshot of the brain.

Alzheimer's is a progressive illness that destroys neurons in the brain initially causing memory loss and eventually dementia. It afflicts some four million older adults in the United States and perhaps three times as many individuals suffer milder forms of the disease that incapacitate memory. It can be diagnosed definitively only after a person dies by an autopsy showing certain brain abnormalities.

Currently, physicians diagnose the disease by evaluating a person's performance on tests of memory and learning, taking a thorough medical and family history, and performing a physical examination. But the disease is difficult to diagnose in its initial stages because there are no definitive laboratory tests.

The new study extends previous findings by Dr. de Leon and other researchers that the hippocampus, another region of the brain associated with memory and learning, diminishes in size as Alzheimer's Disease progresses.

The progressive damage and loss of neurons is one of the hallmarks of Alzheimer's Disease. Previous studies by a German research team indicated that the damage begins in the entorhinal cortex as early as age 30 and spreads to the hippocampus. However, without MRI, this deterioration has been impossible to monitor.

"The entorhinal cortex is the gateway to the hippocampus and is central to all memory functions in the brain," explains Dr. de Leon. "It is a memory distribution and processing center and if its gate is broken, then new memories cannot be made and old memories cannot be retrieved.

In the new study, Dr. de Leon and co-workers developed a new method of measuring the size of the entorhinal cortex based on structural landmarks (called gyri and sulci) which are visible on MRI.

In the first part of the study, the researchers used autopsied brain tissue from Alzheimer's patients and from control subjects who died of conditions unrelated to the brain to establish that the landmarks could be used to define the boundaries of the entorhinal cortex, providing a valid tool for measuring its surface area. The landmark-measurement technique revealed that the entorhinal cortex was reduced by 45% among Alzheimer's patients. In the second part, the researchers used the landmark technique to distinguish patients with very mild Alzheimer's from healthy volunteers. They found that the entorhinal cortex was 27% smaller in patients with very mild Alzheimer's. Moreover, the damage to the entorhinal cortex was greater than to the hippocampus and it proved a more reliable disease marker.

"This is a preliminary study that should be expanded over a period of years to see how brain areas change relative to each other," says Dr. de Leon. "For people with a family history of Alzheimer's, it may be possible to observe such changes and to treat the brain years before there are any signs of memory loss."